Ofloxacin

Therapeutic Class

Fluoroquinolone

Indications

Treatment of complicated urinary tract infections (UTI), uncomplicated skin and skin structure infections (SSSI), acute bacterial exacerbation of chronic bronchitis (ABECB), community-acquired pneumonia (CAP), acute uncomplicated urethral and cervical gonorrhea, nongonococcal urethritis and cervicitis, mixed infections of urethra and cervix, acute pelvic inflammatory disease (PID), uncomplicated cystitis, and prostatitis caused by susceptible strains of microorganisms

Oral
Leprosy
Adult: As part of a multidrug therapy: 400 mg daily or intermittently, depending on regimen.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Oral
Uncomplicated gonorrhoea
Adult: 400 mg as a single dose.
Oral
Acute bacterial exacerbation of chronic bronchitis
Adult: 400 mg bid for 10 days.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Oral
Community-acquired pneumonia
Adult: 400 mg bid for 10 days.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Oral
Uncomplicated skin infections
Adult: 400 mg bid for 10 days.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Oral
Non-gonococcal cervicitis/urethritis due to Chlamydia trachomatis
Adult: 200-300 mg bid for 7 days.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Oral
Mixed infection of the urethra and cervix due to C. trachomatis and Neisseria gonorrhoeae
Adult: 200-300 mg bid for 7 days.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Oral
Pelvic inflammatory disease
Adult: 400 mg bid for 14 days.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Oral
Uncomplicated cystitis
Adult: 200 mg bid for 3 days if due to E. Coli or Klebsiella pneumoniae; 7 days if due to other susceptible organisms.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Oral
Complicated urinary tract infections
Adult: 200 mg bid for 10 days.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Oral
Chronic bacterial prostatitis
Adult: 300 mg bid for 6 wk.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Oral
Traveller's diarrhoea
Adult: 300 mg bid for 1-3 days.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Oral
Postexposure prophylaxis after suspected or confirmed exposure to inhalational anthrax
Adult: 400 mg bid for ≥60 days.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Oral
Legionnaire's disease
Adult: 400 mg bid for 2-3 wk.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Oral
Typhoid fever
Adult: 200-400 mg bid for 7-14 days.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Intravenous
Complicated urinary tract infections
Adult: 200 mg daily by IV infusion over at least 30 min. Max: 400 mg bid infused over at least 1 hr.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Intravenous
Lower respiratory tract infections
Adult: 200 mg bid by IV infusion over at least 30 min. Max: 400 mg bid infused over at least 1 hr.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Intravenous
Septicaemia
Adult: 200 mg bid by IV infusion over at least 30 min. Max: 400 mg bid infused over at least 1 hr.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr.

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Intravenous
Skin and soft tissue infections
Adult: 400 mg bid infused over at least 1 hr.
Renal impairment: Initial dose as normal then reduce.

CrCl (ml/min)	Dosage Recommendation
20-50	Reduce dose by half or give usual dose only every 24 hr.
<20	100 mg every 24 hr

Hepatic impairment: Clearance is reduced in severe hepatic impairment, lower doses should be used. Max: 400 mg daily.
Otic/Aural
Otic infections
Adult: Apply 10 drops of 0.3% solution in the affected ear once daily for 7 days. Lie with the affected ear upwards for 5 min to facilitate penetration into the ear canal.
Child: 6 mth-13 yr: 5 drops of 0.3% solution in the affected ear once daily for 7 days. >13 yr: 10 drops of 0.3% solution in the affected ear once daily for 7 days. Lie with the affected ear upwards for 5 min to facilitate penetration into the ear canal.
Ophthalmic
Bacterial conjunctivitis
Adult: As 0.3% ophth solution: 1-2 drops in the affected eye instilled every 2-4 hr for the first 2 days then 4 times daily for the next 5 days of treatment.
Child: >1 yr: 1-2 drops in the affected eye instilled every 2-4 hr for the first 2 days then 4 times daily for the next 5 days of treatment.
Ophthalmic
Bacterial corneal ulcer
Adult: As 0.3% ophth solution: Days 1-2: Instill 1-2 drops into the affected eye every 30 min while awake. Awaken approximately 4 and 6 hr after retiring and instill 1-2 drops. Days 3-7 (or 9 if necessary): Instill 1-2 drops hrly while awake. Thereafter: Instill 1-2 drops 4 times daily until condition fully resolved.
Child: >1 yr: Days 1-2: Instill 1-2 drops into the affected eye every 30 min while awake. Awaken approximately 4 and 6 hr after retiring and instill 1-2 drops. Days 3-7 (or 9 if necessary): Instill 1-2 drops hrly while awake. Thereafter: Instill 1-2 drops 4 times daily until condition fully resolved.

Special Populations: Reduce dose in patients with renal impairment: CrCl: 20-50 mL/min: 100-200 mg daily or usual dose every 24 hrs; CrCl: <20 mL/min: 100 mg every 24 hrs. Patients undergoing dialysis: 100 mg every 24 hrs.

Contraindications

Hypersensitivity to quinolones; pregnancy and lactation; prolongation of the QT interval; uncorrected hypokalaemia.

Warnings / Precautions

Convulsions, increased intracranial pressure (ICP), toxic psychosis, CNS stimulation, and serious, sometimes fatal, hypersensitivity reactions reported; d/c if any occurs. Rare cases of sensory or sensorimotor axonal polyneuropathy reported; d/c if symptoms of neuropathy occur. Clostridium difficile-associated diarrhea (CDAD) and ruptures of shoulder, hand, and Achilles' tendon reported. Not shown to be effective for syphilis. May result in bacterial resistance with prolonged use or use in the absence of a proven/suspected bacterial infection or a prophylactic indication; take appropriate measures if superinfection develops. Maintain adequate hydration. Caution with renal or hepatic dysfunction, risk for seizures, CNS disorder with predisposition to seizures. Avoid excessive sunlight. Monitor blood, renal and hepatic function with prolonged therapy. D/C immediately at the first appearance of skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted. Drug therapy should be d/c if photosensitivity/phototoxicity occurs. Avoid in patients with known prolongation of the QT interval, and with uncorrected hypokalemia. Caution in elderly taking corticosteroids.

BOXED WARNING: Fluoroquinolones are associated with an increased risk of tendinitis and tendon rupture in all ages. Risk is further increased in patients >60 yrs, taking corticosteroids, and with kidney, heart, or lung transplants. May exacerbate muscle weakness with myasthenia gravis; avoid with known history of myasthenia gravis.

Adverse Reactions

Nausea, vomiting, abdominal pain, diarrhoea; headache, dizziness, insomnia, hallucinations; leucopenia and eosinophilia; vaginitis; dysgeusia; tendon damage and rupture; anorexia; tremor; photosensitivity; hypersensitivity reactions. Discontinue if psychiatric, neurological or hypersensitivity reactions occur.
Potentially Fatal: Anaphylaxis; rarely seizures.

Overdose: Empty stomach, ensure adequate hydration is maintained and observe patient. Treat symptomatically, ofloxacin is not removed efficiently by haemodialysis or peritoneal dialysis.

Drug Interactions

Probenecid decreases elimination. Antacids may reduce ofloxacin absorption, avoid for 2 hr either side of administration. Cimetidine may increase ofloxacin concentrations. Monitor blood glucose in patients on antidiabetic medication.
Potentially Fatal: Corticosteroids may increase risk of tendon rupture. Increases effects of oral anticoagulants, ciclosporin, theophylline. Increased risk of seizures with NSAIDs. Avoid in patients taking QT prolonging medication (e.g. class Ia or III antiarrythmics, astemizole, terfenadine, cisapride, erythromycin, pentamidine, phenothiazines and some TCA).

Lab Interactions

May produce false-positive results for opiates in commercially available urine immunoassay kits.

Food Interactions

Absorption delayed in the presence of food.

Mechanism of Actions

Fluoroquinolone; synthetic broad-spectrum antimicrobial agent; inhibits topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.
Absorption: Rapidly and well absorbed from the GI tract (oral); peak plasma concentrations after 0.5-2 hr. Rate, but not extent, delayed by the presence of food.
Distribution: Widely distributed into body fluids, CSF, tissues, bile (high concentrations); crosses the placenta and enters breast milk. Protein-binding: 20-32%.
Metabolism: <10% of a single dose is metbolised. Converted to desmethyl and N-oxide metabolites; desmethylofloxacin has moderate antibacterial activity.
Excretion: Via urine within 24-48 hr by tubular secretion and glomerular filtration (75-80% as unchanged, <5% as metabolites); via faeces (4-8%). Elimination is biphasic with half-lives of 4-5 hr and 20-25 hr; prolonged in renal impairment (15-60 hr).

Assesment

Assess for risk factors for developing tendinitis and tendon rupture, myasthenia gravis, renal function, LFTs, pregnancy/nursing status, history of seizures, QTc prolongation, and possible drug interactions. Obtain baseline culture and susceptibility test and serologic test for syphilis.

Monitoring

Monitor for tendinitis or tendon rupture, convulsions, increased intracranial pressure, toxic psychosis, CNS events, CDAD, peripheral neuropathy, photosensitivity reactions, and hypersensitivity reactions. Assess renal function and perform follow-up serologic test for syphilis after 3 months

Patient Counselling

Notify physician if experience symptoms of pain, swelling, or inflammation of a tendon, or weakness or inability to move joints; rest and refrain from exercise and d/c therapy. Call physician if muscle weakness or breathing problems worsen. Inform that drug treats bacterial, not viral, infections. Take exactly as directed; skipping doses or not completing full course may decrease effectiveness and increase resistance. Inform about potential benefits/risks. D/C and notify physician if experience skin rash, other allergic reaction, watery or bloody stools, or symptoms of peripheral neuropathy develop. Use caution in activities requiring mental alertness and coordination. Advise diabetic patients to use caution; hypoglycemia may develop during therapy. Inform to take with or without meals, and to drink fluids. Avoid sun exposure.

Administration

May be taken with or without food. (Avoid antacids or supplements containing Fe or Zn w/in 2 hr before or after ofloxacin. Ensure adequate hydration. )

Ophthalmic: Store at 15-25°C.

Oral: Store at 20-25°C.

Otic/Aural: Store at 15-25°C.

Pregnancy Category

C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.